A Phase 2b Study to Evaluate the Efficacy, Safety and PK of a Combination of Bictegravir, Emtricitabine, and Tenofovir Alafenamide Fumarate for Treatment of HIV-1 Infection in Patients With Drug Susceptible-TB on a Rifampicin-based Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 2
- 主要终点
- Number of Participants With Viral Suppression at Week 24
研究概览
简要总结
This study is being conducted to assess the antiretroviral activity of a fixed-drug, single tablet, combination of Bictegravir 50mg/ Emtricitabine 200mg/ Tenofovir alafenamide 25mg (Biktarvy®) dosed twice daily in HIV-1 infected, ART-naïve patients with TB co-infection receiving a rifampicin-based tuberculosis (TB) treatment regimen. This study will assess the activity of Bictegravir and dolutegravir-containing ART regimens in patients with drug-susceptible TB through 48 weeks
详细描述
Primary objective: To characterize viral suppression rates (proportion of patients with suppressed viral load) at week 24 in the BIC arm
Secondary objectives:
To characterize viral suppression rates at weeks 12, 24 and 48 in the standard of care treatment (SOC) arm (currently, TDF 300mg/3TC 300mg/DTG 50mg) and at weeks 12 and 48 in the BIC/FTC/TAF arm.
To compare the pharmacokinetics (PK) of BIC when given twice daily and co-administered with Rifampicin during tuberculosis treatment vs when given alone after discontinuation of Rifampicin
To assess the incidence of TB associated IRIS in each arm, through week 24.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 105 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥ 18 years of age with Karnofsky score ≥ 70
- •Confirmed rifampicin-susceptible tuberculosis and/or
- •On first-line rifampicin-based tuberculosis treatment (not > 8 weeks at the time of enrolment)
- •Documented HIV-1 infection, ART-naïve OR ART non-naïve (patients to have no exposure to ART medication at least ≥ 3 months at the time of enrollment)
- •Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2
- •Alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)
- •Total bilirubin ≤2.5 times ULN
- •Creatinine ≤2 times ULN
- •Hemoglobin ≥ 7.0 g/dL (6.5 g/dL for females)
- •Platelet count ≥ 50,000/mm3
- •Absolute Neutrophil Count (ANC) ≥650/mm3
- •Able and willing to provide written informed consent
- •Female patients agree to use both a barrier and a non-barrier form of contraception during the study, starting at least 14 days prior to enrolment
排除标准
- •Pregnancy or breastfeeding (or planned pregnancy within 12 months of study entry)
- •Prior use of antiretroviral drugs for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) < 3 months at the time of enrolment
- •Hepatitis B surface antigen positive OR Hepatitis B virus (HBV) infection OR active systemic infections (other than HIV-1 infection) requiring systemic antibiotic or antifungal therapy current or within 30 days prior to baseline that could, in the opinion of the investigator, interfere with study procedures or assessment of study outcomes
- •Participants with a CD4+ cell count of < 50 cells/ μl
- •Any verified Grade 4 laboratory abnormality, with the exception of, Grade 4 triglycerides. A single repeat test is allowed during the Screening period to verify a result
- •Patients on metformin (> 500mg, 12hourly)
- •Patients with an uncontrolled psychiatric co-morbidity. Patients who, in the investigator's judgment, pose a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk
- •Other condition or circumstance deemed by clinician/investigators to be detrimental to patient safety or study conduct
- •Unwilling to be part of the main pharmacokinetic (PK) study and have PK blood draws done (NB there is a semi-intensive PK substudy which is optional)
结局指标
主要结局
Number of Participants With Viral Suppression at Week 24
时间窗: Week 24
Viral suppression rate (HIV-1 RNA \<50 copies/mL) at week 24 in the BIC arm (using the FDA snapshot algorithm).
Number of Participants With Viral Suppression at Week 24
时间窗: Week 24
Viral suppression rate (HIV-1 RNA \<50 copies/mL) at week 24 in the BIC arm (using the FDA snapshot algorithm).
次要结局
- Viral Suppression Rates (HIV-1 RNA <50 Copies/mL) at Weeks 12, 24 and 48 in the DTG Arm and at 12 and 48 Weeks in the BIC Arm(Week 12 and 48)
- BIC Drug Concentrations ("Area Under the Plasma Concentration Versus Time Curve (AUC)"(Week 4, 8, 12, 24,32 and 40)
- BIC Drug Concentrations [Peak Plasma Concentration (Cmax)](Week 4, 8, 12, 24, 32 and 40)
- BIC Drug Concentrations [Trough/Minimum Plasma Concentration Ctrough)(Week 4, 8 12, 24, 32 and 40)
- The Incidence of TB Associated IRIS(Through week 24)
- The Tolerability of Treatment in Each Arm(Through week 48)
- Frequency of ART Drug Resistance Mutations in Participants With Detectable Viral Load at Weeks 24 and 48(Week 24 and 48.)
研究者
Anushka Naidoo
Principal Investigator
Centre for the AIDS Programme of Research in South Africa